The Therapeutic Potential of Melatonin in Alzheimer's Disease: A Comprehensive Review.

Alzheimer's Disease (AD) is the most common cause of dementia, afflicting over 5 million people in the United States. There remains a lack of effective diseasemodifying treatments for AD beyond a few approved drugs that provide temporary symptomatic relief. Melatonin is an endogenous hormone mainly produced by the pineal gland that regulates circadian rhythms and possesses antioxidant and anti-inflammatory properties. An expansive body of research over the past few decades has investigated melatonin as a promising therapeutic agent for AD based on its ability to target multiple pathophysiological processes implicated in AD progression. In this comprehensive review, we summarize extensive evidence from cellular and animal models that has uncovered the diverse mechanisms underpinning melatonin's neuroprotective efficacy against AD pathology. We also synthesize clinical studies examining melatonin's effects on AD progression and symptoms. Additionally, we discuss how melatonin's multimodal mechanisms, favorable safety profile, and ability to synergize with conventional therapies heighten its potential as an effective therapeutic strategy for AD. Rigorously designed clinical trials incorporating physiological biomarkers are warranted to definitively establish melatonin's disease-modifying effects. Nevertheless, the considerable preclinical data support further exploration of melatonin as a therapeutic agent for AD.